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1.
Previously, we have demonstrated that chronic-alcohol exposure alters insulin-like growth factor 1 (IGF1) signaling in adult rat heart cells. This report examines the effects of alcohol in vitro on the expression of protein kinase C (PKC) alpha, delta, and epsilon using the embryonic heart cell line, H9c2, and how this may be linked to changes in IGF1 signal transduction. Western blot analyses of H9c2 protein preparations demonstrate that there are significant increases in the total protein levels of PKC delta and epsilon after 4 days exposure to alcohol, and similar increases were found after 2 and 6 days exposure. In addition, there was a significant increase in PKC delta and epsilon in the membranal fractions and a decrease in the cytosolic fractions. No change was found in the expression or activity levels for PKC alpha. Chronic-alcohol exposure (100 mM, 4 days) increased the basal tyrosine kinase activity of the IGF1 receptor (IGF1R), and altered its rate of activation. Chronic-alcohol exposure also reduced the rate of Erk1/Erk2 activation by IGF1. Chronic alcohol blocked the proliferative effects of IGF1 on cell growth and reduced cell viability both in the presence and absence of IGF1, and this alcohol-induced reduction in cell viability was blocked using siRNA to inhibit PKC delta. In addition, a reduction in the amount of myosin light chain 2 was found in the alcohol-exposed cells. In conclusion, chronic alcohol alters PKC delta and epsilon expression and activity, and suppresses the IGF1 signaling pathway in embryonic heart cell culture. Blockage of PKC delta expression using siRNA inhibits the suppressive effects of alcohol on cell viability. 相似文献
2.
Gautham Kulamarva Mark Wilbourn Rajiv Anand Constantinos Mourouzis Anne V Spedding Peter A Brennan 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2007,104(2):240-242
Chordoma is a rare tumor, arising from notochord remnants, which usually occurs in the axial skeleton and rarely metastasizes. Although there have been 3 previous reports of metastatic disease to the facial bones from sacrococcygeal chordoma, this is the first to describe spread to the mandible from a vertebral primary chordoma. 相似文献
3.
Ila Datar Xiaoliang Qiu Hong Zhi Ma Miranda Yeung Shweta Aras Ivana de la Serna Fahd Al-Mulla Jean Paul Thiery Robert Trumbly Xuan Fan Hongjuan Cui Kam C. Yeung 《Oncotarget》2015,6(36):39050-39061
Accumulating evidence suggests that presence of macrophages in the tumor microenvironment add to the invasive and tumor-promoting hallmarks of cancer cells by secreting angiogenic and growth factors. RKIP is a known metastasis suppressor and interferes with several steps of metastasis. However, the mechanistic underpinnings of its function as a broad metastasis suppressor remain poorly understood. Here, we establish a novel pathway for RKIP regulation of metastasis inhibition through the negative regulation of RANTES/CCL5 thereby limiting tumor macrophage infiltration and inhibition of angiogenesis. Using a combination of loss- and gain-of-function approaches, we show that RKIP hinders breast cancer cell invasion by inhibiting expression of the CC chemokine CCL5 in vitro. We also show that the expression levels of RKIP and CCL5 are inversely correlated among clinical human breast cancer samples. Using a mouse allograft breast cancer transplantation model, we highlight that ectopic expression of RKIP significantly decreases tumor vasculature, macrophage infiltration and lung metastases. Mechanistically, we demonstrate that the inhibition of the CCL5 expression is the cause of the observed effects resulting from RKIP expression. Taken together, our results underscore the significance of RKIP as important negative regulator of tumor microenvironment. 相似文献
4.
Abhishek Chaturvedi Randy Lau Gregory Kicska Gautham P. Reddy 《The international journal of cardiovascular imaging》2013,29(1):3-4
Congenital or acquired communication between left ventricle and right atrium is rare and can be easily overlooked as an eccentric tricuspid regurgitation jet. MRI is the ideal modality for accurate diagnosis, providing details for surgical planning about the location and size of the defect. 相似文献
5.
6.
Minjee Kim Sani H. Kizilbash Janice K. Laramy Gautham Gampa Karen E. Parrish Jann N. Sarkaria William F. Elmquist 《Pharmaceutical research》2018,35(9):177
The treatment of metastatic lesions in the brain represents a serious unmet medical need in the field of neuro-oncology. Even though many effective compounds have demonstrated success in treating peripheral (non-CNS) tumors with targeted agents, one aspect of this lack of success in the brain may be related to poor delivery of otherwise effective compounds. Many factors can influence the brain delivery of these agents, but one key barrier is a heterogeneously “leaky” BBB that expresses efflux transporters that limit the BBB permeability for many targeted agents. Future success in therapeutics for brain metastases must take into account the adequate delivery of “active, free drug” to the target, and may include combinations of targeted drugs that are appropriate to address each individual patient’s tumor type. This review discusses some issues that are pertinent to precision medicine for brain metastases, using specific examples of tumor types that have a high incidence of brain metastases. 相似文献
7.
Yoram Burak Ila R. Fiete 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(43):17645-17650
Neural noise limits the fidelity of representations in the brain. This limitation has been extensively analyzed for sensory coding. However, in short-term memory and integrator networks, where noise accumulates and can play an even more prominent role, much less is known about how neural noise interacts with neural and network parameters to determine the accuracy of the computation. Here we analytically derive how the stored memory in continuous attractor networks of probabilistically spiking neurons will degrade over time through diffusion. By combining statistical and dynamical approaches, we establish a fundamental limit on the network’s ability to maintain a persistent state: The noise-induced drift of the memory state over time within the network is strictly lower-bounded by the accuracy of estimation of the network’s instantaneous memory state by an ideal external observer. This result takes the form of an information-diffusion inequality. We derive some unexpected consequences: Despite the persistence time of short-term memory networks, it does not pay to accumulate spikes for longer than the cellular time-constant to read out their contents. For certain neural transfer functions, the conditions for optimal sensory coding coincide with those for optimal storage, implying that short-term memory may be co-localized with sensory representation. 相似文献
8.
Gautham Ravipati M.D. Wilbert S. Aronow M.D. Albert J. De Luca M.D. Tamana Walia M.D. John A. McClung M.D. Robert N. Belkin M.D. 《The International journal of angiology》2005,14(3):138-140
We investigated in 335 patients (mean age-63 year) with suspected myocardial ischemia the prevalence of moderate or severe
left ventricular diastolic dysfunction (LVDD) in patients with an abnormal adenosine or exercise sestamibi stress test (SST)
or prior coronary revascularization and in patients with a normal SST and no prior coronary revascularization. Moderate or
severe LVDD was present in 117 of 142 patients (82%) with an abnormal SST or prior coronary revascularization and in 111 of
193 patients (58%) with a normal SST and no prior coronary revascularization (p < 0.001). Moderate or severe LVDD was present in 34 of 38 patients (89%) with an abnormal SST or prior coronary revascularization
and an abnormal left ventricular ejection fraction (LVEF) and in 4 of 8 patients (50%) with a normal SST and no prior coronary
revascularization and an abnormal LVEF (p < 0.01). 相似文献
9.
Enes Elvin Gul MD Rajiv A. Kabadi MD Santosh K. Padala MD Paula Sanchez Somonte MD Jordana Kron MD Richard K. Shepard MD Jayanthi N. Koneru MD Gautham Kalahasty MD Maria Terricabras MD Bernice Tsang MD Yaariv Khaykin MD Zaev Wulffhart MD Alfredo Pantano MD Kenneth A. Ellenbogen MD Atul Verma MD 《Journal of cardiovascular electrophysiology》2021,32(9):2515-2521
10.
Elsayed Mohammad Cheng Bernard Xing Minzhi Sethi Ila Brandon David Schuster David M. Bercu Zachary Galt James Barron Bruce Kokabi Nima 《Cardiovascular and interventional radiology》2021,44(2):254-260
CardioVascular and Interventional Radiology - To compare lung shunt fraction (LSF) prior to Y-90 radioembolization calculated using planar imaging versus SPECT/CT in patients with hepatocellular... 相似文献